Multifunctional liposomes remodeling tumor microenvironment for enhancing Hemoporfin‐mediated photodynamic therapy

Abstract

Abstract Photodynamic therapy (PDT) utilizes light and photosensitizer (PS) to generate reactive oxygen species (ROS) to kill cancer cells, presenting a promising strategy as an anti‐cancer treatment. However, the low hydrophilicity and poor targeting of currently used PSs, as well as the abnormal tumor microenvironment (TME), limit the clinical application of PDT. Herein, non‐toxic liposomes with the ability to incorporate both hydrophilic and hydrophobic PS are used as the nanocarrier to co‐load Hemoporfin, L‐buthionine sulfoximine (BSO), and catalase (CAT) to obtain BSO/CAT@Liposomes‐Hemoporfin nanoparticles (BCHL NPs), which could be used to remodel the TME and to enhance Hemoporfin‐mediated PDT efficacy. BCHL NPs exhibit a long blood circulation time and can accumulate in the tumor. BSO can reduce the cytosolic concentration of glutathione (GSH), a natural scavenger of ROS. CAT catalyzes the endogenously overexpressed H 2 O 2 in the tumor site into H 2 O and O 2 , thus relieving tumor hypoxia and enhancing ROS generation. Upon irradiation, the synergetic effects of reduced GSH synthesis by BSO and relieved hypoxia by CAT were observed in 4T1 tumor‐bearing mouse model. Compared to the tumor treated by free Hemoporfin, BCHL NPs‐mediated PDT resulted in 1.25‐fold higher inhibition of tumor growth due to the enhanced ROS generation. The present study provides insight into the design of efficient strategies for enhanced clinic Hemoporfin‐mediated PDT efficiency.